Genetic Testing in Human: The Clinician’s Perspective http://www. ncbi

Genetic Testing in Human Molecular genetic testing in patient care GeneTests Essential elements of testing for clinicians

Uses of Molecular Genetic Testing To help physicians provide the best medical care for a patient with an inherited disorder To help a person with an inherited disorder make informed personal decisions

Molecular Genetic Testing: a.Medical Care Diagnostic testing in symptomatic persons Predictive testing in asymptomatic persons when treatment is available

Medical Care: a1.Symptomatic Person Establish a diagnosis (e.g., Huntington disease: HD gene testing is the only way to make the diagnosis with certainty) Confirm a diagnosis (e.g., HNPCC: MLH1/MSH2 testing in a person who does not quite meet Amsterdam criteria)

Medical Care: a2.At-risk Asymptomatic Person Predictive testing: Identify family members who have the disease-causing mutation before symptoms appear so that they can be monitored for early signs of the disease and treated promptly to reduce morbidity and mortality (e.g., HNPCC)

33 y Proband HNPCC 50% risk Indeterminate risk 28 y 65 y 40 y 13 y

Molecular Genetic Testing: b.Personal Decision-making* Carrier testing: Autosomal recessive disorders Predictive testing: No treatment available Prenatal diagnosis/Preimplantation genetic diagnosis (PGD) *Results of testing do not help medical care

Genetic Testing Molecular genetic testing in clinical practice: BASIC PRINCIPLES GeneTests Clinical testing: Essential elements for clinicians

www.genetests.org

GeneReviews: “User manual” for genetic testing for specific diseases One new Review added each week Laboratory Directory: “Yellow Pages” of genetics labs ~610 Clinical and research laboratories ~1460 Inherited diseases ~1180 clinical tests ~280 research only Illustrated Glossary: Genetic counseling and testing terms

Molecular genetic testing: Testing used in patient care must be done in “clinical” laboratories, not research laboratories Clinical laboratories have to meet standards set by federal law (“BHP”)

GeneReviews Useful to all clinicians regardless of availability of molecular genetic testing Provide to non-expert clinicians information on the diagnosis, management and genetic counseling of patients with inherited disorders and their families Expert-authored, peer-reviewed, updated regularly

GeneReviews: Search by Disease

GeneReviews: Search by Disease HNPCC

GeneReviews: Disease Search Result Clinical Testing Research Testing GeneReview Consumer Oriented Resources

GeneReviews: Search by Title

GeneReviews: Search by Title

GeneReviews: HNPCC Disease search result: Select Reviews button Title search result: Select HNPCC from the list Hereditary Motor and Sensory Neuropathy with Agenesis of the Corpus Callosum Hereditary Neuropathy with Liability to Pressure Palsies Hereditary Non-Polyposis Colon Cancer Hereditary Sensory Neuropathy Type I Hereditary Spastic Paraplegia Overview

GeneReviews Content Summary Diagnosis Clinical Description Differential Diagnosis Management Genetic Counseling Molecular Genetics Resources References

GeneReviews Summary One paragraph on: Disease characteristics Diagnosis/testing Management Genetic counseling

GeneReviews Diagnosis Clinical Diagnosis Testing Molecular genetic testing Testing strategy (Order in which to use all the testing described above for diagnosis)

GeneReviews Clinical Description Natural History What are the clinical findings in this disorder? What happens over time to people who have this condition? How does the disease progress?   

GeneReviews Differential Diagnosis What other conditions are similar to this condition?

GeneReviews Management Evaluations Following Initial Diagnosis Treatment of Manifestations Prevention of Primary Manifestations Prevention of Secondary Complications Surveillance Agents/Circumstances to Avoid Testing of Relatives at Risk Therapies Under Investigation

GeneReviews Genetic Counseling Risk to Family Members Parents of a proband Sibs of a proband Offspring of a proband Prenatal Testing

Genetic Testing Molecular genetic testing in clinical practice: BASIC PRINCIPLES GeneTests: EASY TO USE Essential elements of genetic testing for clinicians

Genetic Testing: Essential Elements for Clinicians Educational materials about the disease and the test Test result report forms that explain the test and the patient’s test result Collection of data on phenotype and genotype

Essential Elements: Educational Materials What is the test? What is the test used for? Who should be tested? What does a positive test result mean for the patient? What does a negative test result mean for the patient?

Essential Elements: Test Result Report Forms Clinical Indication: Why is the test being performed? Results: Normal, abnormal, uncertain Interpretation: What do results mean for this patient? Limitations: What can’t the test do? Suggestions for test result clarification: Testing other family members, other tests to do Test methods: How was this test performed? Resources: Links or citations to help the clinician understand more about the disease or test References: Literature citations

Genetic Testing: Data Collection A one page (electronic) phenotype data collection form to be filled in by the clinician at the time the test is ordered. Must be anonymous to protect the patient. Central database for phenotype data and genotype data when testing is completed

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